GLP-1 RECEPTOR AGONISTS IN HUMAN CANCERS: A NARRATIVE LITERATURE REVIEW

The relationship between GLP-1 receptor agonists (GLP-1RAs) - including exenatide, liraglutide, dulaglutide, semaglutide, and the dual GIP/GLP-1 agonist tirzepatide - and cancer risk in humans is profound. As thirteen malignancies have been epidemiologically classified as obesity-associated cancers (OACs), and GLP-1RAs produce substantial weight loss and the GLP-1 receptor (GLP-1R) is expressed across many tumor types, GLP-1 agonists should be investigated for direct anti- neoplastic properties.
GLP-1 agonists beneficial effects concern hepatocellular carcinoma, colorectal cancer, endometrial cancer, ovarian cancer, meningioma, gallbladder cancer, and multiple myeloma, with risk reductions in the range of HR 0.35-0.76 in large cohorts versus insulin. Pancreatic, gastric, and esophageal cancers now appear neutral to mildly favorable, and the initial concern regarding pancreatic cancer has been dispelled for the time. Breast cancer appears neutral-to-favourable, supported by direct anti-tumor mechanisms demonstrated in cell lines. In thyroid and kidney cancer data remains unclear whereas cholangiocarcinoma and neuroendocrine neoplasms remain points of conflicting evidence.